According to the World Health Organization (WHO), it is considered that joint diseases are a major cause of disability in the modern era; in addition such disorders are alarmingly increasing. In the particular case of the United States of America, according to a study conducted in 2010 by the Center for Disease Control and Prevention, approximately 48 million people in this country suffer some joint disease, representing an increase of approximately 3 million people in the last three years. Unfortunately, because of the aging of the population, it is estimated that by the year of 2030 there will be an increase of approximately 40% in the number of people suffering of some type of joint diseases, so that about 67 million people will be affected.
Among the most common joint diseases, one can find rheumatoid arthritis, osteoarthritis, fibromyalgia and gouty arthritis. These diseases are closely related with the presence of pain, which is considered a debilitating symptom of said disease, causing suffering and disability. Chronic or episodic pain is the main cause of loss of function and mobility of joints. In addition to joint pain, other symptoms are inflammation and stiffness of the affected joints.
In general, joint conditions do not cause the death of people. However, it is considered that the greatest impact of these diseases occur in the quality of life of people, causing disability, loss of independence, decreasing in the number of social interactions, distress and decreased well-being of people who suffer this kind of diseases. In this regard, in the United States of America, it is estimated that direct and indirect medical costs associated with these diseases are approximately 128 billion dollars each year.
As it was previously mentioned, the most important joint diseases are rheumatoid arthritis; which is a chronic, recurring and systemic disease that mainly affects diarthrodial joints corresponding to the extremities that have important mobility. Arthritis occurs more frequently in women than in men by a ratio of 3:1, in which the constitutional symptoms include malaise, fever and weight loss.
Most currently treatments that are used to relieve the pain caused by joint diseases have several disadvantages, such as limited effectiveness and the appearance of undesirable side effects.
In the case of conventional treatment for rheumatoid arthritis, the objective is treating the patient in the earliest and most effective possible manner, while having the lowest toxicity. Something similar is done with the person affected by osteoarthritis, but this disease has an evolution time that is longer in comparison with that of rheumatoid arthritis. To do this, there are used the so-called disease modifying drugs (DMARDs) such as gold salts, synthetic antimalarials, the inmunoreductors or immunosuppressive and anti-tumor necrosis factor (TNF) inhibitors and interleukin (IL biological products. However, the uses of these drugs also cause adverse side effects in the patient, or are too expensive. For example, gold salts cause dermatitis and stomatitis, besides they have a metallic taste; while antimalarials cause razor burn, leucopenia, and peripheral neuropathy, among other adverse effects.
On the other hand, the biological agents, such as chimeric monoclonal antibodies and recombinant fusion proteins are used to increase production of anti-inflammatory cytokines or to inhibit proinflammatory cytokines, have a very good activity and low toxicity; nevertheless, their main disadvantage is that they have a significantly high cost.
In brief words, although there have been significant advances in the understanding and treatment of joint diseases, particularly rheumatoid arthritis, it is not expected a cure for these diseases in the near future, consequently patients will continue suffering the effects of the disease, in which pain is a main symptom.
From the above, nowadays there is a continuous search for alternative drugs that effectively help in the treatment of joint diseases, such as the use of phytodrugs or medicaments comprising extracts of various plant species as their components.
Among those plant species that have been used to relieve various types of pain due to its components, it can be mentioned Arnica montana (arnica), Rosmarinus officinalis (rosemary), Zingiber officinale (ginger) and Boswellia serrata (boswellia).
The rnica plant is a perennial herbaceous species belonging to the family Compositae. Arnica is useful in relieving all kind of contusions and bruises as well as muscular and rheumatic pain, among other uses. This plant has a moderate toxicity, so its use is only recommended in an external manner. Within its chemical composition, it can be mentioned flavonoids (astragaloside, isoquercitroside and quercetin-3-gluco-galacturonic aid); carotenes (zeaxanthin); essential oils (caffeic, chlorogenic, thymol, florol, polyacetylenic compounds arnidiol, faradiol, teraxasterol), fixed oils (glycerides of palmitic, oleic and lauric), resins (containing cytisine and gallic acid), alkaloids (arnicina), acetylenic derivatives (betaine and choline), arnicolide A and sesquiterpene lactone (helenalin and dihydrohelenalin), and other compounds.
Among said compounds, flavonoids exert antispasmodic and hypotensive properties. Carotenoids and manganese provides antineuralgic, antirheumatic, anti-inflammatory and anti-echimotic effects. While essential oils have antibacterial and nervous sedative results. It is known that sesquiterpene lactones have anti-inflammatory effects, especially those with α-methylene-φ-lactonic structure. The biological effects of these substances are mediated by immune processes. The most active of these substances is helenalin, to which the use of arnica for pain and inflammation is due.
On the other hand, the prior art has reported that rosemary presents analgesic properties acting against migraine and headaches; muscle, back, hips and bones pain, bruises, rheumatism and inflammation of joints, rosemary has been used as an antispasmodic and has healing properties, among others properties. Rosemary has, in its chemical composition, the presence of flavonoids (hesperidoside, cirsimarine, diosmine, apigenine, luteolin), diterpenic derivatives (rosmaridiphenol, carnosol, carnosic acid; rosmanol, rosmadial, ursolic acid and amyrin), essential oils (cineol, camphene, camphor, borneol), phenolic acids (rosmarinic, caffeic, chlorogenic acid), alkaloids (rosmaricine) and minerals (sodium, potassium, calcium, magnesium, iron, copper, zinc and manganese) among other components.
Likewise, some studies indicate that rosmarinic acid inhibits lipooxygenase activity in the cascade mechanism of arachidonic acid, so that the anti-inflammatory effects of rosemary may be due to the diminished formation of prostaglandins and leukotrienes and induction of D-galactosamine, consequently the formation of peroxynitrite is inhibited which provokes said anti-inflammatory effect.
On the other hand, the active compounds of ginger exhibit activity on the biosynthesis of prostaglandins, besides this plant have effects on arachidonate 5-lipoxygenase that synthesizes leukotrienes. In vitro studies have shown that a ginger extract inhibits the activity of cyclooxygenase and lipoxygenase in the cascade mechanism of the arachidonic acid; it is considered that their anti-inflammatory effects may be due to a diminished formation of prostaglandins and leukotrienes. Ginger also acts as a potent inhibitor of thromboxane synthetase, raising levels of prostacyclin and increasing E2 and F2a prostaglandin. Among the components presents in the ginger extract, it could be mentioned (6)-shogaol which inhibits carrageenan-induced rat paw edema due to cyclooxygenase activity inhibition, while gingerol has an inhibitory effect on the biosynthesis of prostaglandins as PG2, which is involved in inflammatory processes.
Finally, boswellia has analgesic and anti-inflammatory effects similar to non-steroidal anti-inflammatory drugs (NSAIDs). The anti-inflammatory effect of boswellia's resin is attributed to the presence of boswellic acids that inhibit two proinflammatory enzymes, namely, 5-lipoxygenase and human leukocyte elastase (HLE). Boswellic acids increase blood flow to the joints and restore the integrity of the vessels obstructed by spasms; boswellia constitutes an appropriate therapy in cases of stiffness, pain and decreased strength of joints caused by arthritis.
In addition, in the prior art, there are disclosed compositions including among their components any of the plant species above mentioned, but they are combined with other plants. For example, U.S. Pat. No. 5,494,668 describes a composition comprising extracts of Withania somnifera, Boswellia serrata, Curcuma longa and Zingiber officinale; this composition is preferably for enteral administration and is useful in treating rheumatoid arthritis and osteoarthritis.
Furthermore, U.S. Pat. No. 6,534,086 discloses a composition for the treatment of pain and inflammation caused by joint diseases, among other conditions, the composition consists of a boswellic acid and a curcuminoid, and may further contain other compounds such as gingerol preferably derived from a botanical source.
It is further cited U.S. Pat. No 7,923,038, which discloses a composition for topical application to treat joint conditions, the composition is formulated in a water-based gel without alcohol, this composition comprises various herbal extracts, including arnica and rosemary, which in this specific case, is used to repair tendons, ligaments and damaged soft tissues.
Finally, international publication No. WO2010/068264 describes a formulation for oral administration comprising herbal extracts of Withania somnifera, Boswellia serrata, Curcuma longa and Zingiber officinale. This formulation is used to alleviate symptoms associated with cyclooxygenase, pro-inflammatory cytokines or pro-inflammatory enzyme conditions, including rheumatoid arthritis and osteoarthritis.
As it can be observed, in the prior art there are various herbal preparations used to treat joint diseases and symptoms associated therewith. Nevertheless, none of said preparation discloses or suggests a synergistic composition as that of the present invention to be used to treat muscle, arthritic and rheumatic pain associated with joint diseases, the composition being effective and of low cost as well as it lacks of those adverse side effects associated with allopathic drugs.